5-180618911-G-T

Variant names:

• chr5-180618911-G-T
• NM_182925.5:c.2860C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182925.5(FLT4):​c.2860C>A​(p.Pro954Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,433,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P954S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FLT4 NM_182925.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.79

Genes affected

FLT4 (HGNC:3767): (fms related receptor tyrosine kinase 4) This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23091757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.2860C>A	p.Pro954Thr	missense_variant	Exon 21 of 30	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.2860C>A	p.Pro954Thr	missense_variant	Exon 21 of 30	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433582 Hom.: 0 Cov.: 34 AF XY: 0.00000141 AC XY: 1 AN XY: 710598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.0079	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Uncertain	0.57	D;.;D
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.99	L;L;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.21
Sift	Benign	0.047	D;T;D
Sift4G	Uncertain	0.041	D;T;T
Polyphen		0.036	B;.;B
Vest4		0.37
MutPred		0.42		Gain of phosphorylation at P954 (P = 0.0057);Gain of phosphorylation at P954 (P = 0.0057);Gain of phosphorylation at P954 (P = 0.0057);
MVP		0.41
MPC		1.1
ClinPred		0.65	D
GERP RS		4.0
Varity_R		0.24
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-180045911;